2.02012-05-31 13:59:09 -06002015-09-13 12:56:13 -0600ECMDB03431M2MDB000502L-HistidinolL-Histidinol is a structural analogue of the essential amino acid L-histidine. It is an intermediate in histidine metabolism. It is converted to L-histidinal via bifunctional histidinal dehydrogenase/histidinol dehydrogenase (EC:1.1.1.23). (KEGG)(S)-b-amino-1H-Imidazole-4-propanol(S)-beta-Amino-1H-imidazole-4-propanol(S)-β-amino-1H-Imidazole-4-propanolHistidinolHistidolHSOImidazole C-4(5) deriv. 4L-histidinolC6H11N3O141.171141.090211989(2S)-2-amino-3-(1H-imidazol-5-yl)propan-1-olHSO4836-52-6N[C@H](CO)CC1=CN=CN1InChI=1S/C6H11N3O/c7-5(3-10)1-6-2-8-4-9-6/h2,4-5,10H,1,3,7H2,(H,8,9)/t5-/m0/s1ZQISRDCJNBUVMM-YFKPBYRVSA-NSolidCytosollogp-1.10logs-0.00solubility1.40e+02 g/llogp-1.7pka_strongest_acidic13.45pka_strongest_basic9.41iupac(2S)-2-amino-3-(1H-imidazol-5-yl)propan-1-olaverage_mass141.171mono_mass141.090211989smilesN[C@H](CO)CC1=CN=CN1formulaC6H11N3OinchiInChI=1S/C6H11N3O/c7-5(3-10)1-6-2-8-4-9-6/h2,4-5,10H,1,3,7H2,(H,8,9)/t5-/m0/s1inchikeyZQISRDCJNBUVMM-YFKPBYRVSA-Npolar_surface_area74.93refractivity38.19polarizability14.74rotatable_bond_count3acceptor_count3donor_count3physiological_charge2formal_charge0Histidine metabolismec00340Metabolic pathwayseco01100Secondary Metabolites: Histidine biosynthesisHistidine biosynthesis starts with a product of PRPP biosynthesis pathway, phosphoribosyl pyrophosphate which interacts with a hydrogen ion through an ATP phosphoribosyltransferase resulting in an pyrophosphate and a phosphoribosyl-ATP. This compound interacts with water through a phosphoribosyl-AMP cyclohydrolase / phosphoribosyl-ATP pyrophosphatase resulting in the release of pyrophosphate, hydrogen ion and a phosphoribosyl-AMP. This enzyme proceeds to interact with phosphoribosyl-AMP and water resulting in a 1-(5'-Phosphoribosyl)-5-amino-4-imidazolecarboxamide. This compound is then isomerized by a N-(5'-phospho-L-ribosyl-formimino)-5-amino-1-(5'-phosphoribosyl)-4-imidazolecarboxamide isomerase resulting in a PhosphoribosylformiminoAICAR-phosphate. This compound reacts with L-glutamine through an imidazole glycerol phosphate synthase resulting in a L-glutamic acid, hydrogen ion, 5-aminoimidazole-4-carboxamide and a D-erythro-imidazole-glycerol-phosphate. This compound reacts with a imidazoleglycerol-phosphate dehydratase / histidinol-phosphatase, dehydrating the compound and resulting in a imidazole acetol-phosphate.
This compound interacts with L-glutamic acid through a histidinol-phosphate aminotransferase, releasing oxoglutaric acid and L-histidinol-phosphate. The latter compound interacts with water and a imidazoleglycerol-phosphate dehydratase / histidinol-phosphatase resulting in L-histidinol and phosphate. L-histidinol interacts with a NAD-driven histidinol dehydrogenase resulting in a Histidinal. This in turn reacts with water in a NAD driven histidinal dehydrogenase resulting in L-Histidine.
L-Histidine then represses ATP phosphoribosyltransferase, regulation its own biosynthesis.PW000984Metabolichistidine biosynthesisHistidine biosynthesis starts with a product of PRPP biosynthesis pathway, phosphoribosyl pyrophosphate which interacts with a hydrogen ion through an ATP phosphoribosyltransferase resulting in an pyrophosphate and a phosphoribosyl-ATP. This compound interacts with water through a phosphoribosyl-AMP cyclohydrolase / phosphoribosyl-ATP pyrophosphatase resulting in the release of pyrophosphate, hydrogen ion and a phosphoribosyl-AMP. This enzyme proceeds to interact with phosphoribosyl-AMP and water resulting in a 1-(5'-Phosphoribosyl)-5-amino-4-imidazolecarboxamide. This compound is then isomerized by a N-(5'-phospho-L-ribosyl-formimino)-5-amino-1-(5'-phosphoribosyl)-4-imidazolecarboxamide isomerase resulting in a PhosphoribosylformiminoAICAR-phosphate. This compound reacts with L-glutamine through an imidazole glycerol phosphate synthase resulting in a L-glutamic acid, hydrogen ion, 5-aminoimidazole-4-carboxamide and a D-erythro-imidazole-glycerol-phosphate. This compound reacts with a imidazoleglycerol-phosphate dehydratase / histidinol-phosphatase, dehydrating the compound and resulting in a imidazole acetol-phosphate.
This compound interacts with L-glutamic acid through a histidinol-phosphate aminotransferase, releasing oxoglutaric acid and L-histidinol-phosphate. The latter compound interacts with water and a imidazoleglycerol-phosphate dehydratase / histidinol-phosphatase resulting in L-histidinol and phosphate. L-histidinol interacts with a NAD-driven histidinol dehydrogenase resulting in a Histidinal. This in turn reacts with water in a NAD driven histidinal dehydrogenase resulting in L-Histidine.
L-Histidine then represses ATP phosphoribosyltransferase, regulation its own biosynthesis.PW000810Metabolichistidine biosynthesisHISTSYN-PWYSpecdb::CMs847Specdb::CMs848Specdb::CMs849Specdb::CMs850Specdb::CMs3340Specdb::CMs30204Specdb::CMs30310Specdb::CMs30597Specdb::CMs30792Specdb::CMs38600Specdb::CMs163783Specdb::NmrOneD1970Specdb::NmrOneD4949Specdb::NmrOneD4950Specdb::NmrOneD21882Specdb::NmrOneD21883Specdb::NmrOneD21884Specdb::NmrOneD21885Specdb::NmrOneD21886Specdb::NmrOneD21887Specdb::NmrOneD21888Specdb::NmrOneD21889Specdb::NmrOneD21890Specdb::NmrOneD21891Specdb::NmrOneD21892Specdb::NmrOneD21893Specdb::NmrOneD21894Specdb::NmrOneD21895Specdb::NmrOneD21896Specdb::NmrOneD21897Specdb::NmrOneD21898Specdb::NmrOneD21899Specdb::NmrOneD21900Specdb::NmrOneD21901Specdb::MsMs2307Specdb::MsMs2308Specdb::MsMs2309Specdb::MsMs5947Specdb::MsMs5948Specdb::MsMs5949Specdb::MsMs5950Specdb::MsMs5951Specdb::MsMs5956Specdb::MsMs179958Specdb::MsMs179959Specdb::MsMs179960Specdb::MsMs182292Specdb::MsMs182293Specdb::MsMs182294Specdb::MsMs446315Specdb::MsMs446316Specdb::MsMs446317Specdb::MsMs446318Specdb::MsMs446319Specdb::MsMs448034Specdb::MsMs2227347Specdb::MsMs2227387Specdb::MsMs2229672Specdb::MsMs2231983Specdb::NmrTwoD1905HMDB03431165271144886C0086016255HISTIDINOLKeseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590.21097882Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114.22080510Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948.18331064Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599.19561621Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4.19212411Raju RV, Datla RS, Warrington RC, Sharma RK: Effects of L-histidine and its structural analogues on human N-myristoyltransferase activity and importance of EEVEH amino acid sequence for enzyme activity. Biochemistry. 1998 Oct 20;37(42):14928-36.9778369Warrington RC, Cheng I, Zhang L, Fang WD: L-histidinol increases the vulnerability of cultured human leukemia and lymphoma cells to anticancer drugs. Anticancer Res. 1993 Nov-Dec;13(6A):2107-12.8297120Warrington RC, Norum JN, Hilchey JL, Watt C, Fang WD: A simple, informative, and quantitative flow cytometric method for assessing apoptosis in cultured cells. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Apr;27(2):231-43.12657362Beltra, A. P.; Bonete, P.; Gonzalez-Garcia, J.; Garcia-Garcia, V.; Montiel, V. Electrochemical synthesis of L-histidinol using solvated electrons. Journal of the Electrochemical Society (2005), 152(4), D65-D68.http://hmdb.ca/system/metabolites/msds/000/003/012/original/HMDB03431.pdf?1358461610Histidine biosynthesis bifunctional protein hisBP06987HIS7_ECOLIhisBhttp://ecmdb.ca/proteins/P06987.xmlHistidinol dehydrogenaseP06988HISX_ECOLIhisDhttp://ecmdb.ca/proteins/P06988.xmlWater + L-Histidinol + 2 NAD >3 Hydrogen ion + L-Histidine +2 NADHWater + Histidinol phosphate <> L-Histidinol + PhosphateR03013HISTIDPHOS-RXNL-Histidinol + NAD <> L-Histidinal + NADH + Hydrogen ionR03012Histidinol phosphate + Water > L-Histidinol + PhosphateHISTIDPHOS-RXNL-Histidinol + NAD > Hydrogen ion + histidinal + NADHHISTOLDEHYD-RXNHistidinol phosphate + Water > L-Histidinol + Inorganic phosphateL-Histidinol + Water + 2 NAD > L-Histidine +2 NADHL-Histidinol + 2 NAD + Water <> L-Histidine +2 NADH +3 Hydrogen ionR01158 L-histidinol-phosphate + Water > Phosphate + L-HistidinolPW_R002872L-Histidinol + NAD > NADH + Hydrogen ion + HistidinalPW_R002873Water + Histidinol phosphate <> L-Histidinol + PhosphateWater + Histidinol phosphate <> L-Histidinol + PhosphateGutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L glucoseShake flask and filter culture12.8uM0.037 oCK12 NCM3722Mid-Log Phase512000Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599.19561621Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L glycerolShake flask and filter culture19.2uM0.037 oCK12 NCM3722Mid-Log Phase768000Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599.19561621Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L acetateShake flask and filter culture19.6uM0.037 oCK12 NCM3722Mid-Log Phase784000Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599.19561621